TRUNCATED MEMAPSIN 2 COMPOSITIONS AND TREATMENTS

• US 20090214554A1
• Filed: 09/17/2008
• Published: 08/27/2009
• Est. Priority Date: 08/10/2005
• Status: Abandoned Application

• Current Assignee: Oklahoma Medical Research Foundation
• Original Assignee: Oklahoma Medical Research Foundation
• Inventors: Tang, Jordan J.N., Downs, Deborah, CHANG, Wan Pin
• Application Number:
  US12/212,539
• Publication Number:
  US 20090214554A1
• Time in Patent Office: Days
• US Class Current: 424/139.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/488 Aspartic endopeptidases (3.4.23), e.g. pepsin, chymosin, renin, cathepsin E
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C12N 9/6421 from mammals

Abstract

The present invention provides novel methods of reducing memapsin 2 β-secretase activity in a subject, decreasing levels of β-amyloid peptide in the brain of a subject, treating Alzheimer'"'"'s disease and/or reducing the size and/or number of β-amyloid plaques in the brain of a subject. The methods may include the step of administering an effective amount of truncated memapsin 2 protein, anti-truncated memapsin 2 antibody, and/or nucleic acid encoding a truncated memapsin 2 protein or anti-truncated memapsin 2 antibody. The present invention also provides related pharmaceutical compositions and uses thereof.

Claims

1. A method of reducing memapsin 2 β

-secretase activity to treat a disease associated with memapsin 2 β

-secretase activity in a subject in need of such treatment, the method comprising administering to said subject an effective amount of a truncated memapsin 2 protein, and wherein said truncated memapsin 2 protein consists of amino acids 63-454 of FIG. 4, optionally containing at least one conservative amino acid substitution.

2. The method of claim 1, wherein said subject is a mammal.

3. The method of claim 2, wherein said subject is a human.

4. The method of claim 1, wherein said disease is Alzheimer'"'"'s disease.

10. The method of claim 1, wherein said truncated memapsin 2 protein consists of amino acids or 63-454 of FIG. 4.

5-9. -9. (canceled)

11. A method of decreasing levels of β

-amyloid peptide in the brain of a subject, said method comprising administering to said subject an effective amount of a truncated memapsin 2 protein, and wherein said truncated memapsin 2 protein consists of amino acids 63-454 of FIG. 4, optionally containing at least one conservative amino acid substitution, and said truncated memapsin 2 protein reduces memapsin 2 β

-secretase activity in said subject.

12. A method of reducing the size or number of β

-amyloid plaques in the brain of said subject, said method comprising administering to said subject an effective amount of a truncated memapsin 2 protein, and wherein said truncated memapsin 2 protein consists of amino acids 63-454 of FIG. 4, optionally containing at least one conservative amino acid substitution, and said truncated memapsin 2 protein reduces memapsin 2 β

-secretase activity in said subject.

13. A method of treating Alzheimer'"'"'s disease in a patient in need of such treatment, said method comprising administering to said subject an effective amount of a truncated memapsin 2 protein, and wherein said truncated memapsin 2 protein consists of amino acids 63-454 of FIG. 4, optionally containing at least one conservative amino acid substitution, and said truncated memapsin 2 protein reduces memapsin 2 β

-secretase activity in said subject.

14. An antibody specifically immunoreactive with a truncated memapsin 2 protein, and wherein said truncated memapsin 2 protein consists of amino acids 63-454 of FIG. 4, optionally containing at least one conservative amino acid substitution, and said antibody reduces memapsin 2 β

-secretase activity.

15. The antibody of claim 14, wherein said antibody is an isolated antibody.

16. The antibody of claim 14, wherein said antibody is a monoclonal antibody.

17. The antibody of claim 14, wherein said antibody is an antibody fragment.

18. The antibody of claim 14, wherein said antibody is a humanized antibody.

19. A pharmaceutical composition comprising the antibody of claim 14 and a pharmaceutically acceptable excipient.

20. A pharmaceutical composition comprising a truncated memapsin 2 and a pharmaceutically acceptable adjuvant, wherein said truncated memapsin 2 protein consists of amino acids 63-454 of FIG. 4, optionally containing at least one conservative amino acid substitution.

21. A pharmaceutical composition comprising a nucleic acid encoding a truncated memapsin 2 and a pharmaceutically acceptable excipient, wherein said truncated memapsin 2 protein consists of amino acids 63-454 of FIG. 4, optionally containing at least one conservative amino acid substitution.

22. An antibody specifically immunoreactive with a truncated memapsin 2 protein, and wherein said truncated memapsin 2 protein consists of amino acids 63-454 of FIG. 4, optionally containing at least one conservative amino acid substitution, and said antibody reduces Aβ

production.